A large body of evidence indicates that pharmacologically active lymphokines produced by antigen stimulation of immune lymphocytes regulate and amplify immune responses as well as the destruction associated with some disease states. Recent studies have now suggested that the gingival and bone destruction characteristic of periodontal disease are caused by lymphokines produced by dental plaque stimulation of immune thymus (T) and bone marrow (B) derived lymphocytes. Evidence for this presumption has been limited to qualitative tissue culture studies of lymphokine activities. This proposal seeks to elucidate and define the role(s) of one lymphokine, human leukocyte migration inhibition factors (MIF) in periodontal disease. Efforts will be made to quantitate the in vitro plaque induced MIF production by immune T and B cells as well as by assessing MIF levels in diseased gingival biopsy specimens in relation to the clinical severity of periodontal disease in the donor. The initial experimental thrust will be to isolate and purify MIF from T and B cell culture supernatants by the isoelectric focusing technique (IEF). Secondly, these purified preparations will be used for immunization to induce specific anti-MIF lymphokine antibodies. These antibodies will provide an immunologic tool to quantitatively assay the amount of MIF produced by plaque stimulated lymphocyte cultures and in gingival tissue. The feasibility of the proposed methodology has been confirmed by the principal investigators during participation in the successful isolation and characterization of human T and B lymphocyte derived monocyte chemotactic lymphokines. Also there are plans to investigate the functional role of MIF in plaque induced T and B cell primary and secondary responses associated with periodontal disease.